For patients with early-stage Hodgkin’s lymphoma, forgoing radiotherapy after three cycles of chemotherapy when PET scans show negative findings – known as a PET-directed or response-adapted approach – was not found to be noninferior to routine consolidation radiotherapy in extending progression-free survival, according to a report published online April 23 in the New England Journal of Medicine.
The PET-directed technique is intended to spare the estimated 9 out of 10 patients who are cured by the chemotherapy from having to receive unnecessary radiotherapy, which carries late toxic effects such as secondary cancers and premature cardiovascular disease. To determine whether this approach caused an unacceptable increase in the relapse rate, researchers performed a randomized, controlled, phase III noninferiority trial in 602 previously untreated patients aged 16-75 years (median age, 34 years) who had stage IA or IIA Hodgkin’s lymphoma with no mediastinal bulk and no night sweats, unexplained fever, or weight loss, reported Dr. John Radford of the Institute of Cancer Sciences, University of Manchester (England), and his associates.
The study participants, enrolled and treated at 94 medical centers across the United Kingdom, had three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine therapy and then underwent PET scanning. The 420 who had negative findings on PET then were randomly assigned to receive either 30 Gy of involved-field radiotherapy (209 patients) or no further treatment (211 patients).
After a median of 62 months of follow-up, both groups had excellent outcomes. Three-year progression-free survival was 94.6% with radiotherapy and 90.8% without it; overall survival was 97.1% with radiotherapy and 99.0% without it. However, the modest advantage conveyed by radiotherapy in the 3-year progression-free survival rate – 3.8 percentage points in the intention-to-treat analysis and 6.3 percentage points in the per-protocol analysis – was enough to negate a finding of noninferiority for forgoing radiotherapy, the investigators wrote (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1408648]).
It is important to note that this marginal survival advantage “is bought at the expense of exposing all patients to radiation, most of whom will not benefit and some of whom will be harmed,” Dr. Radford and his associates wrote.
This report addressed medium-term outcomes. Continued follow-up in this ongoing study will determine whether the response-adapted approach leads to fewer second cancers, less cardiovascular disease, and superior survival in the long term, they added.